OXiGENE, Inc, a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer and eye diseases, announced that it has begun a pivotal registration study of its first-in-class vascular disrupting agent, Zybrestat (combretastatin-A4 phosphate/CA4P), in patients with metastatic anaplastic thyroid cancer (ATC).
The multinational, randomized and controlled, phase II/III study is being conducted under a Special Protocol Assessment agreement with the US Food and Drug Administration (FDA) and is expected to enrol approximately 180 patients at about 45 sites in the United States, Eastern and Western Europe, Asia, and the Middle East.
According to a company press release, two-thirds of the patients will be administered intravenous Zybrestat plus carboplatin and paclitaxel, and the other third will receive carboplatin and paclitaxel alone. The primary endpoint will be a statistically significant difference in the overall survival rate between the two treatment arms, as determined by a log-rank analysis of Kaplan-Meier survival curves at times when pre-determined numbers of study events (patient deaths) are reached. The study design incorporates a planned interim analysis for efficacy and safety, which will be overseen by an Independent Data Monitoring Committee. Zybrestat has been granted Fast Track status by the FDA and Orphan Drug status by both the FDA and the European Agency for the Evaluation of Medicinal Products (EMEA).
"The initiation of this pivotal study last week represents a major advancement in the Company's efforts to bring Zybrestat to market," said Richard Chin, M.D., chief executive officer of OXiGENE. "There is a tremendous need for effective treatment options for patients suffering from anaplastic thyroid cancer, and this pivotal registration study is based on a significant body of encouraging preclinical and clinical data that suggest that the combination of Zybrestat, carboplatin, and paclitaxel has activity against anaplastic thyroid cancer and other solid tumors."
ATC is one of the most lethal cancers known in humans. There are no approved treatments for this disease. ATC is a high-grade neoplasm, characterized by an aggressive clinical course with brief survival, and refractoriness to currently available local and systemic modalities of treatment. ATC comprises 1-2% of all thyroid malignancies in the United States, and up to 5% in certain countries outside the United States. While ATC epidemiology has not been extensively studied and documented, it is estimated that there are approximately 1,000 to 4,000 new cases per year in the U.S. and in Europe combined. Newly-diagnosed ATC patients have a median life expectancy of approximately 3 months, and only a very limited number of patients survive for longer than one year.
The company believes that Zybrestat is poised to become the first therapeutic product in a novel class of small-molecule drug candidates called vascular disrupting agents (VDAs). Through interaction with vascular endothelial cell cytoskeletal proteins, Zybrestat selectively targets and collapses tumour vasculature, thereby depriving the tumour of oxygen and causing death of tumour cells. Zybrestat has demonstrated potent and selective activity against tumour vasculature, as well as clinical activity against ATC and other solid tumours in clinical studies.
A Special Protocol Assessment (SPA) is an agreement with the U.S. Food and Drug Administration that the Company's Phase II/III clinical trial design is sufficient to form the basis for a regulatory approval, if pre-specified efficacy results are achieved. The SPA process allows for FDA evaluation of a clinical trial protocol intended to form the primary basis of an efficacy claim in support of a New Drug Application (NDA).